Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic Apc(Min/+) Mice, Correlating with CB1 Receptor Up-Regulation

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Abstract

Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of Apc(Min/+) mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the "protective" action of the CB1 receptor is lost.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume18
Issue number3
DOIs
Publication statusPublished - Feb 24 2017

Fingerprint

Polyunsaturated fatty acids
Cannabinoid Receptor CB1
fatty acids
Unsaturated Fatty Acids
mice
Tumors
Up-Regulation
tumors
Olive oil
Tissue
cancer
Gene expression
Growth
gene expression
Neoplasms
adipose tissues
Genes
Cells
Gene Expression
oils

Keywords

  • Animal Feed
  • Animals
  • Colorectal Neoplasms
  • Disease Models, Animal
  • Fatty Acids, Omega-3
  • Gene Expression
  • Genes, APC
  • Humans
  • Intestinal Mucosa
  • Mice
  • Mice, Transgenic
  • Neoplasms
  • Receptor, Cannabinoid, CB1
  • Xenograft Model Antitumor Assays
  • Journal Article

Cite this

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title = "Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic Apc(Min/+) Mice, Correlating with CB1 Receptor Up-Regulation",
abstract = "Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of Apc(Min/+) mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the {"}protective{"} action of the CB1 receptor is lost.",
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author = "Maria Notarnicola and Valeria Tutino and {De Nunzio}, Valentina and Francesco Dituri and Caruso, {Maria Gabriella} and Gianluigi Giannelli",
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AU - Notarnicola, Maria

AU - Tutino, Valeria

AU - De Nunzio, Valentina

AU - Dituri, Francesco

AU - Caruso, Maria Gabriella

AU - Giannelli, Gianluigi

PY - 2017/2/24

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N2 - Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of Apc(Min/+) mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the "protective" action of the CB1 receptor is lost.

AB - Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis. Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of Apc(Min/+) mice. To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC). Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway. Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the "protective" action of the CB1 receptor is lost.

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KW - Fatty Acids, Omega-3

KW - Gene Expression

KW - Genes, APC

KW - Humans

KW - Intestinal Mucosa

KW - Mice

KW - Mice, Transgenic

KW - Neoplasms

KW - Receptor, Cannabinoid, CB1

KW - Xenograft Model Antitumor Assays

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